Arrangement and method for preserving the new-boneforming effect of growth-stimulating substances for an implant product

ABSTRACT

In an arrangement and method, use is made of a container for preserving, even for a long time, the new-bone-forming effect of growth-stimulating substances (GS) applied to one or more implant products. The container is arranged so as, dependent on being acted upon, to allow accessibility of the product concerned with applied GS as the time of its use. The container is arranged to enclose the product or the products with applied GS in an environment which is essentially free from air, water and moisture. The container functions as a vacuum container, and the storage times for GS can be extended considerably in relation to previously used arrangements and methods.

The present invention relates to an arrangement for a container forpreserving, even for a long time, the new-bone-forming effect ofgrowth-stimulating substances (GS) applied to one or more implantproducts. In this connection, the container is arranged so as, dependenton being acted upon, to allow accessibility of the product concernedwith applied GS at the time of use of the product. Here, long timemeans, for example, periods of several years.

It has previously been proposed that a GS which is intended to be usedon implants, for example dental implants, should be kept in a frozenenvironment until use on the spot by a surgeon, dentist etc. The user inquestion should then mix the frozen molecules with an aqueous solutionin order to achieve an appropriate concentration which is to be appliedto the product/the implant in question at the point of use. It has alsobeen proposed that the molecules be applied to the product and that thecombination of molecules/product be frozen during storage and transport.

Achieving the correct concentration and correct application with thecorrect application technique on the product in question in order toarrive at a desired result with regard to new-bone growth in the dentalcontext is difficult and requires extensive experience and knowledge. Inorder to avoid incorrect use sur place, it has become desirable for theconcentration and application techniques to be performed in the factoryand for the product provided with GS to be supplied in finished state tothe location where the dental work is to be carried out. In thisconnection, the need exists to manufacture products with GS in thefactory and to effect interim storage of the products in connection withsale and distribution to the users. The object of the present inventionis to resolve inter alia this problematic situation and to start fromthe knowledge the storage time for the GS applied to the product ishighly dependent on whether or not the GS is exposed to air, water or amoist environment. In this respect, the greater the exposure of the GSto air, water and moisture, the shorter will be the storage time inorder for effective use of the product in question with GS to bepossible. The invention also aims to solve this problem by makingpossible long storage times in this connection, that is to say storagetimes of several years.

An arrangement according to the invention can be considered to becharacterized mainly in that the container is arranged to enclose theproduct or the products with applied GS in an environment which isessentially free from air, water and moisture.

In this connection, the container can be in the form of a glass ampoule,or be made of metal which makes the environment free from air, water andmoisture possible, for example metal in the form of titanium, stainlesssteel etc. The container can consist of a vacuum container which has aninternal pressure for the product or the products with applied GS of<10⁻⁴ mbar. Said environment can comprise one or more essentially inertgases, for example argon, nitrogen or helium, which in one embodimentare used in connection with evacuation of the container in question.

A method according to the invention can be considered to becharacterized mainly in that the container is made to enclose theproduct or the products with applied GS in an environment which isessentially free from air, water and moisture. In one embodiment, theproduct with associated GS can, be applied in a glass tube provided witha bottom, the interior of which is connected to a vacuum pump. Afterevacuation, a burning means employed can be activated for formation of aclosed glass ampoule by sealing the glass tube part enclosing theproduct with GS. In the case of metal, a first part or lower part madeof foil-shaped metal, for example titanium or stainless steel, can beused. The product is arranged on the first part with associated GSapplied. A second part or upper part likewise made of foil-shaped metalis applied to the first part or lower part with the product or theproducts enclosed. The space between the parts which is intended for theproduct or the products is evacuated and/or filled with gas and sealedby means of laser welding or what may be referred to as extendedsingle-spot welding, that is to say welding by means of one stroke alongthe entire sealing length. In some applications, seaming can also beemployed as the sealing method. Other developments of the method emergefrom the subsequent subclaims for the method.

By virtue of what is proposed above, accurate production of optimumproducts loaded or provided with GS can take place in the factory. Evenafter a long storage time, the product with GS can give optimum resultswith regard to new-bone growth in various dental situations. As examplesof GS, mention may be made of matrix molecules, growth anddifferentiation factors and peptides with growth-stimulating properties.GS can also be applied to substances such as autologous bone, allogenicbone or synthetic preparations, these substances and preparations alsothen having a long storage time with the principle employed. When aircontaining water and moisture is replaced by inert gas free from wateror moisture or evacuation of the container concerned is effected, knownequipment can be used for the gas supply and evacuation.

A for the present proposed arrangement and method based on thecharacteristics significant of the invention will be described belowwith simultaneous reference to accompanying drawings in which

FIG. 1 shows in the form of a schematic diagram the formation of a glassampoule with a product provided with GS introduced, the interior of theglass ampoule being connectable to on the one hand a vacuum pump and onthe other hand a gas bottle;

FIG. 1 a shows in principle the sealing function for the glass ampoule;

FIG. 1 b shows in principle a pumping arrangement for a number ofampoules;

FIG. 2 shows a horizontal view of a first part or lower part made ofmetal foil with a compartment for an implant or another product withapplied GS;

FIG. 3 shows a vertical section of the first part or lower partaccording to FIG. 2;

FIG. 4 shows a horizontal view from above of a second part or upper partintended to be applied to the first part or lower part and provided witha tear-off strip for uncovering the product with applied GS enclosed bythe first and second parts;

FIG. 5 shows a side view of the upper part according to FIG. 4;

FIG. 6 shows a horizontal view of the first and second parts in an ajoined-together state, the parts having been joined together by means ofa welding procedure, and

FIG. 7 shows a side view of a part of the welding tool for extendedsingle-spot welding which brings about the mutual sealing of the firstand second parts with the implant with GS located inside.

In FIG. 1, what will become a glass ampoule is indicated symbolically by1. A vacuum pump of a kind known per se is shown by 2 and a gascontainer by 3. The ampoule is connected to a line system 4 which isindicated schematically. The connection of the interior 1 a of the glassampoule to the line system is effected by means of melting the glassmaterial. Also connected to the system is a manometer 6 in order to makeit possible to establish an appropriate pressure in the system. The pump2 is connected to the line system via valve means 7. The gas bottle 3 isprovided with a regulating valve 8, to which a manometer, here calledthe second manometer 9, can be connected. The gas bottle arrangement canbe connected to the line system 4 via a second valve means 9′. A productindicated schematically, for example an implant, which has the referencenumber 11, is introduced into the glass ampoule. The product is providedwith GS in the manner indicated in the applications filed by the sameapplicant and inventor. In this connection, reference may be made topatent applications WO 00/72775 and WO 00/72777 by the same applicant asin the present patent application. Reference may also be made to thearticle “Properties of a New Porous Oxide Surface on Titanium Implants,Volume 1: The Oxidized Titanium Surface, Applied OsseointegrationResearch”, October 2000, published by among others the inventoraccording to the present patent application.

A technique known per se can be used for sealing the ampoule 1. By meansof the vacuum pump, the interior of the ampoule is evacuated to a valuewhich is <10⁻⁴ in the illustrative embodiment. In the space 10, theglass ampoule thus evacuated is sealed with the aid of a rotating burner12 according to FIG. 1. The burner works with a gas flame 13. The glassampoule 1 is provided with a sealed bottom part 1 b, and the top part 1c is also sealed by means of the gas flame 13. As the glass ampoule isprovided with an indication, it can then be opened by breaking. In somecases, it is desirable for the glass ampoule to be provided with apositive pressure by an inert gas, for example argon, in order toprevent glass fragments entering the ampoule when it is broken. Theampoule is then filled with gas from the gas bottle 3 which is connectedvia the regulating valve 8 and the valve means 9 to the line system andvia the connection valve 5.

FIG. 1 shows a multiple arrangement for a number of glass ampoules. Eachglass ampoule 15, 16, 17, 18, 19, 20, 21 and 22 is connected internallyto a line 23, which can in turn be connected in a manner known per se tosaid gas bottle 3 and the vacuum pump. Products provided with GS can beintroduced into the ampoules, after which the latter can be evacuated,filled with gas and sealed in accordance with the above.

FIGS. 2-7 show the case when the container consists of two foil-shapedmetal parts which can be welded together with one another with theproduct with GS located inside during simultaneous evacuation of thespace for the product in connection with evacuation. FIG. 2 shows afirst part or lower part 24 with a space 25 for a product in the form ofan implant 26 which has been coated with GS on its external-thread 26 ain the way indicated above. The space 25 can contain more than oneproduct, which has been symbolized by 27.

FIG. 3 shows the shape of the first part or lower part from the side;the part can be regarded as comprising a space part 28 and a flange part29.

FIG. 4 shows a second part or upper part which is intended to be joinedtogether with the part according to FIGS. 2 and 3. The second part orupper part is indicated by 30 and is provided with a tear-off strip 31.The second part or upper part is arranged in a vacuum-tight manner inrelation to the lower part by means of welding around the flange part,for example laser welding. The tear-off strip has at one of its ends atab 31 a, by means of which it is possible to take hold of the strip andtear the same off from the part 30 in question.

In accordance with FIG. 5, the tab part 31 a has a shape which is easyto grip and facilitates tearing-off of the flap 31 from the part 30.

FIG. 6 shows the case where the second part 30 has been applied to thefirst part 24. Sealing is effected by means of laser welding or thewelding stamp 32 shown symbolically in FIG. 7 which is arranged toestablish a vacuum-tight seal 33 between the parts 24 and 30 byinteraction. Sealing is effected at the flange 29 shown in FIG. 3.Sealing is effected by a single interaction between the stamp and theparts 30 and 40, and the welding function is referred to here asextended single-spot welding. Stamping is preceded by evacuation and insome cases by a subsequent gas-filling of the inner space (compare 25 inFIG. 3) of the parts, which evacuation and gas-filling are performed ina symbolically indicated apparatus 34 of a type known per se. Referenceis also made to the arrangement above according to FIGS. 1-1 b. The weld33 runs all the way round and on the whole follows the center line ofthe flange 29. The container 35 thus evacuated makes possible long-termstorage of the product 26 with applied GS for said long time without theGS degenerating with regard to its new-bone-forming function.

The invention is not limited to the embodiment shown above by way ofexample but can undergo modifications within the scope of the followingpatent claims and the inventive idea.

1. An arrangement for a container for preserving the new-bone-formingeffect of growth-stimulating substances (GS) applied to at least oneimplant product, the container being arranged so as, dependent on beingacted upon, to allow access to the at least one implant product withapplied GS at the time of use of the at least one implant product withapplied GS, wherein the container is arranged to enclose the at leastone implant product with applied GS in an environment which isessentially free from air, water and moisture.
 2. The arrangement ofclaim 1, wherein the container is in the form of a glass ampoule.
 3. Thearrangement of claim 1, wherein the container is made of metal whichmakes the environment free from air, water and moisture possible.
 4. Thearrangement of claim 1, wherein the container has been evacuated to aninternal pressure less than 1 mbar.
 5. The arrangement of claim 1,wherein said environment comprises at least one essentially inert gasesfree from air, water and moisture.
 6. A method for a container forpreserving the new-bone-forming effect of growth-stimulating substances(GS) applied to at least one implant product, comprising: enclosing theat least one implant product with applied GS in a container thatprovides an environment which is essentially free from air, water andmoisture, wherein the container is arranged to be openable, dependent onbeing acted upon, so as to allow access to the at least one implantproduct with applied GS at the time of use of the at least one implantproduct.
 7. The method of claim 6, wherein the container is made as aglass ampoule or of metal capable of preserving the environment freefrom air, water and moisture.
 8. The method of claim 6, wherein thecontainer is evacuated with an internal pressure of less than 1 mbar. 9.The method of claim 6, wherein the environment free from air, water andmoisture is formed by means of one or more gases free from water andmoisture.
 10. The method of claim 6, wherein the at least one implantproduct with applied GS is introduced into an open glass ampoule, theinterior of which is connected to a vacuum pump, and wherein, when a lowinternal vacuum pressure has been reached, the glass ampoule is sealedusing a burning means.
 11. The method of claim 10, wherein the at leastone implant product with applied GS is introduced into a glass tubeprovided with a bottom, wherein the interior of the glass tube isconnected to the vacuum pump, and wherein the burning means is activatedfor formation of a closed glass ampoule by sealing a glass tube partenclosing the at least one implant product with applied GS.
 12. Themethod of claim 10, wherein the interior of the ampoule or of the glasstube part is connected temporarily to a gas container.
 13. The method ofclaim 6, wherein the at least one implant product with applied GS isarranged in a first part made of foil-shaped metal, wherein a secondpart made of foil-shaped metal is applied to the first part and over theat least one implant product, and wherein a space between the first andsecond parts which is intended for the at least one implant product orthe with applied GS is evacuated and/or filled with gas and sealed bymeans of extended single-spot welding or laser welding.
 14. The methodof claim 13, wherein at least one of the first part and the second partis made with a tear-off foil strip for access to the at least oneimplant product with applied GS at the time of use.
 15. The arrangementof claim 3, wherein the metal is titanium or stainless steel.
 16. Thearrangement of claim 1, wherein the container has been evacuated to aninternal pressure of less than 10⁻³ mbar.
 17. The arrangement of claim5, wherein the at least one essentially inert gas is argon.
 18. Thearrangement of claim 7, wherein the metal is titanium or stainlesssteel.
 19. The arrangement of claim 6, wherein the container isevacuated with an internal pressure of less than 10⁻³ mbar.
 20. Themethod of claim 10, wherein the burning means is a rotating burner. 21.The method of claim 13, wherein the first part is a lower part and thesecond part is an upper part.